Allogeneic γ9δ2 T Cells Treatment of Recurrent Hematologic Tumors

NCT05755854 | Unknown Phase 1

• 1 other identifier: QH10103-M-01（0）
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open single-arm clinical study aimed at evaluating the safety and tolerance of allogeneic γ9δ2 T cell injection in the treatment of patients with recurrent hematologic tumors after allogeneic hematopoietic stem cell transplantation.

Conditions

Hematologic Diseases

Keywords

Recurrent hematologic tumors; Allogenic γδT Cell

Outcome Measures

Primary Outcomes (4)

• Incidence of Adverse Events (AEs)

  AE is defined as any adverse medical event from the date of leukapheresis to 12 months after allogeneic γ9δ2 T cells infusion. Among them, cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) were graded according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria, graft-versushost disease (GVHD) according to criteria defined by the Mount Sinai Acute GVHD International Consortium. Other AEs were graded according to common terminology criteria for adverse events (CTCAE) v5.0

  12 months

• Incidence of Dose-Limiting Toxicities (DLTs)

  DLT was defined as allogeneic γ9δ2 T Cells-related events with onset within first 14 days following infusion: The development of Grade (G) III-IV acute GVHD according to the Mount Sinai Acute GVHD International Consortium criteria; The development of G3 or higher grade CRS lasting \> 2 weeks; Any allogeneic γ9δ2 T cells-related AE requiring intubation; All G4 non-hematologic toxicities. Symptoms of GVHD include but are not limited to skin rash, enterocolitis with diarrhea, liver dysfunction with jaundice, fever, weight loss, etc.

  First infusion date of allogeneic γ9δ2 T cells to 14 days end cell infusion

• Maximum tolerated dose (MTD)

  MTD is defined as the highest dose level of less than or equal to 2 DLT among the 6 subjects finally determined.

  14 days

• Recommended phase 2 dose (RP2D)

  The recommended dose for phase 2 was determined through phase 1 study

  14 days

Secondary Outcomes (4)

• Overall Survival (OS)

  12 months

• Progression Free Survival (PFS)

  12 months

• Pharmacokinetics: Persistence of the allogeneic γ9δ2 T cells

  14 days

• Pharmacodynamics: Peak level of cytokines in serum

  14 days

Study Arms (1)

Patients with recurrent hematologic tumors after allogeneic hematopoietic stem cell transplantation

EXPERIMENTAL

A conditional chemotherapy regimen of fludarabine and cyclophosphamide will be administered, zoredronic acid depending on the patient's status, followed by investigational therapy, allogeneic γ9δ2 T Cells

Biological: allogeneic γ9δ2 T Cells; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Zoredronic acid

Interventions

allogeneic γ9δ2 T Cells BIOLOGICAL

dose escalation (3+3) : dose 1 (5 × 10\^7cells/kg) ,dose 2 (1 × 10\^8 cells/kg) ,dose 3 (2 × 10\^8cells/kg)

Patients with recurrent hematologic tumors after allogeneic hematopoietic stem cell transplantation

Fludarabine DRUG

Intravenous fludarabine on days-5 and -4,the infusion dose is adjusted according to the subject's condition

Also known as: Fludarabine Phosphate for Injection

Patients with recurrent hematologic tumors after allogeneic hematopoietic stem cell transplantation

Cyclophosphamide DRUG

Intravenous cyclophosphamide on days -5、-4、and -3, the infusion dose is adjusted according to the subject's condition

Also known as: Cyclophosphamide for Injection

Patients with recurrent hematologic tumors after allogeneic hematopoietic stem cell transplantation

Zoredronic acid DRUG

Intravenous zoredronic acid 50ug/kg 24 hours before cell infusion（or according to the dosage of the instruction）（If applicable）

Patients with recurrent hematologic tumors after allogeneic hematopoietic stem cell transplantation

Eligibility Criteria

• Age: 12 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 12-65 (inclusive)；
• Patients with recurrent hematologic tumors after allogeneic hematopoietic stem cell transplantation；
• Basically normal liver and kidney function (as demonstrated by the following laboratory tests prior to initial γ9δ2 T cell therapy)
• Alanine transaminase/aspartate transaminase \< 2.5×ULN；
• serum creatinine \< 1.5×ULN；
• total bilirubin level \< 1.5×ULN；
• No obvious hereditary disease;
• Normal cardiac function, cardiac ejection index above 55%;
• Women of reproductive age (15 to 49 years) must undergo a pregnancy test within 7 days before starting treatment and the result is negative, and use contraception during the clinical trial period and within 3 months after the last cell transfusion;
• Sign informed consent.

You may not qualify if:

• Patients with simple extramedullary recurrence;
• Pregnant and lactating women;
• Organ failure;
• Heart: Ⅲ level and Ⅳ level;
• Liver: reach the grade C Child - Turcotte liver function;
• Kidney, renal failure and uremia period;
• Lung: symptoms of severe respiratory failure;
• Brain: consciousness disorder.
• Patients with a history of solid organ transplantation;
• Uncontrollable infectious diseases or other serious diseases, including but not limited to infections (such as HIV positive), congestive heart failure, unstable angina, arrhythmia, psychosis, or restricted social circumstances or those that the attending physician considers to pose unpredictable risks;
• Patients with systemic autoimmune diseases or primary immunodeficiency;
• Patients with allergic constitution;
• Use of systemic steroid drugs;
• Chronic diseases requiring the use of immunological agents or hormone herapy;
• Prior treatment with any other immune cells;

Sponsors & Collaborators

• Anhui Provincial Hospital: lead

Study Sites (1)

Anhui Provincial Hospital

Hefei, Anhui, 230036, China

RECRUITING

MeSH Terms

Conditions

Hematologic Diseases

Interventions

fludarabine; fludarabine phosphate; Injections; Cyclophosphamide

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Zhu Xiaoyu, Ph.D

  Director of Hematology Department, Anhui Provincial Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhu Xiaoyu, Ph.D

CONTACT

+86 15255456091; xiaoyuz@ustc.edu.cn

Sun Guangyu

CONTACT

+86 13956970687; sunguangyu_vip@foxmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Hematology Department

Study Record Dates

• First Submitted: February 23, 2023
• First Posted: March 6, 2023
• Study Start: May 3, 2023
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2025
• Last Updated: September 22, 2023

Record last verified: 2023-09

Locations

CN (1)